Is ADPGK p.Ala2Val (c.5C>T) pathogenic?

ADPGK p.Ala2Val (c.5C>T) is classified Uncertain significance in ADPGK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.000356%, nfe).

How common is ADPGK p.Ala2Val (c.5C>T) in the general population?

ADPGK p.Ala2Val (c.5C>T) is very rare (popmax 0.000356%, nfe) (gnomAD).

ADPGK p.Ala2Val

c.5C>T · VCV4019637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000356%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.176	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 215 bp · p 0.0013 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000356% European (non-Finnish) · 4/1,122,846 alleles

Filtering AF 8.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.6e-05%

Overall 0.00027% 4/1,481,824 alleles · very rare exomes 3/1,329,594 · genomes 1/152,230 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADPGK
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_001365225
Type: single nucleotide variant
Location: chr15:72783687 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36

Full ADPGK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADPGK p.Ala146Val Uncertain significance ★ same type
ADPGK p.Ala318Thr Uncertain significance ★ same type
ADPGK p.Ala318Val Uncertain significance ★ same type
ADPGK p.Ala416Thr Uncertain significance ★ same type
ADPGK p.Ala429Val Uncertain significance ★ same type
ADPGK p.Ala58Val Uncertain significance ★ same type
ADPGK p.Ala59Val Uncertain significance ★ same type
ADPGK p.Ala63Ser Uncertain significance ★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/adpgk-p-ala2val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown